Stable liquid formulations of antibodies are useful for parenteral administration, such as intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) administration. Such formulations must fulfill two key requirements: 1) the required drug concentration must be achieved, and, 2) the drug must be chemically and physically stable in order to have a sufficient shelf-life.
For a protein to remain biologically active, a formulation must preserve intact the Conformational integrity and at the same time the protein's multiple functional groups must be protected from degradation. Degradation pathways for proteins can involve chemical instability or physical instability. For example, chemical instability can result from deamidation, hydrolysis oxidation, beta-elimination or disulfide exchange, while physical instability can result from denaturation, aggregation, precipitation or adsorption, for example. Aggregation is one of the most common protein degradation pathways.
Most current stable formulations of antibodies are not liquid formulations. For example, WO97/04801 describes a stable lyophilized formulation of anti-IgE antibodies. The stability of proteins in aqueous formulations is of general importance to the pharmaceutical industry. The problem has been addressed by drying the protein, for example, by the method of freeze-drying. For a patient who needs daily injections of an antibody, it is of importance that the product is easy to handle, to dose and inject. Because a dried antibody formulation is then distributed and stored in dried form, the patient or medical professional has to reconstitute the dried powder in a solvent before use, which is an inconvenience for the patient.
Thus, it is advantageous to provide a liquid antibody formulation for which reconstitution before use is not required.
Furthermore, the freeze-drying process is a costly and time consuming process, and it would be advantageous if this step could be avoided when preparing a commercial antibody formulation.
It would also be advantage for the manufacture and formulation of a therapeutical product if the final pharmaceutical solution contained only few or no additives.
Thus, there is a demand on the market for stable, liquid, injectable antibody formulations; and, in particular, for highly concentrated stable, liquid, injectable antibody formulations.
There is also a need for stable aqueous solutions comprising a high concentration of antibody protein that can be used as a starting material or intermediate in process to obtain stable liquid antibody formulations of the invention.